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Research for immunodysregulation and acquisition of autoimmunity induced by silica compounds

Research Project

Project/Area Number 09670500
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKAWASAKI MEDICAL SCHOOL

Principal Investigator

OTSUKI Takemi  Kawasaki Med.Sch.Medical School, Associate Professor, 医学部, 助教授 (40160551)

Co-Investigator(Kenkyū-buntansha) KAWAKAMI Yasuhiko  Kawasaki Med.Sch.Medical School, Research Associate, 医学部, 助手 (10234030)
TOMOKUNI Akiko  Kawasaki Med.Sch.Medical School, Research Associate, 医学部, 助手 (30278957)
UEKI Ayako  Kawasaki Med.Sch.Medical School, Professor, 医学部, 教授 (10069031)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordssilica compound / silicosis / Fas / Fas ligand / apoptosis / caspase / alternative splicing / Fas ligahd
Research Abstract

We have been studying the immunodysregulation and acquisition of autoimmunity induced by silica compounds and have observed following findings ; i) increase of relative expression of soluble Fas as compared with membrane Fas message in peripheral blood mononuclear cells (PBMC) from silicosis cases (SIL), ii) No difference of total Fas or Fas ligand expression between SIL and healthy volunteers (HV), iii) elevation of serum soluble Fas in SIL, iv) No difference of membrane Fas on the surface of peripheral blood lymphocytes (PBL), v) NO difference of serum soluble Fas ligand, v) induction of apoptosis of PBMC cultured with silica compound, chrysotile B, vi) inhibition of this apoptosos by addition of antibodies for Fas/Fas ligand pathway, and anti-caspase 8 neutralizing antibody, vii) upregulatlon of Fas, Fas ligand, caspase, 1, 3, and 8 genes during apoptosis induced by silica, viii) stronger inducibility of apoptosis by silica than man-made mineral fibers, ix) detection of alternatively spliced variant messages in PBMC from SIL.
These findings indicate that lymphocytes which are resistant to the silica-induced apoptosis will appear during exposure of silica compounds occupationally and chronically, although healthy lymphocytes easily enter the Fas-mediated apoptosis pathway and die after activation due to silica exposure. These resistant clones may include subpopulation of self-reccgnizing clones and they may produce soluble Fas which may antagonize with membrane Fas to bind with Fas ligand and make self-recognize clones to survive longer. These clones may possess an important role to acquire autoimmunity in cases with silicosis.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Otsuki T et al.: "Soluble Fas mRNA is dominantly expressed in cases with silicosis" Immunology. 94(2). 258-262 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tomokuni A at al.: "Elevated soluble Fas/APO-1(CD95)levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours." Clinical and Experimental Immunol. 110(2). 303-309 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aikoh T et al.: "Activation-induced cell death in human periphcral blood lymhpocytes after stimulation with silicate in vitro" International Journal of Oncology. 12(6). 1355-1359 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hyodoh F et al.: "Release of IL-8 from human monocytes by asbestos" Kawasaki Medial Journal. 24(3-4). 1-10 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Otsuki T et al.: "Soluble Fas message is dominantly expressed in cases with silicosis" Advances in the Prevention of Occup Resp Dis Excerpta Medica International Congress Serles ICS. 1153. 896-900 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tomokuni A at al: "Elevated soluble Fas levels in patients with sillcosis" Advances in the Prevention of Occup Resp Dis Excerpta Medica International Congress Serles ICS. 1153. 931-936 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Otsuki T et al.: "Soluble Fas mRNA is dominantly expressed in cases with silicosis" Immunol. 94(2). 258-262 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tomokuni A et al.: "Elevated soluble Fas/APO-1 (CD95) levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours" Clin Exp Immunol. 110(2). 303-309 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aikoh T et al.: "Activation-induced cell death in humna peripheral blood lymhpocytes after stimulation with silicate in vitro" Int J Oncol. 12(6). 1355-1359 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hyodho F et al.: "Release of IL-8 from human monocytes by asbestos" Kawasaki Med J. 24(3-4). 1-10 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Otsuki T et al.: "Sokuble Fas message is dominantly expressed in cases" Advances in the Prevention of Occup Resp Dis Excerpta Medical International with silicosis Congress Series ICS. 1153. 896-900 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tomokuni A et al.: "Elevated soluble Fas levels in patients with silicosis" Advances in the Prevention of Occup Resp Dis Excerpta Medica International Congress silicosis Series ICS. 1153. 931-936 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Otsuki T et al.: "Soluble Fas mRNA is dominantly expressed in cases with silicosis" Immunology. 94(2). 258-262 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomokuni A et al.: "Elevated soluble Fas/APO-1(CD95)levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours" Clinical and Experimental Immunology. 110(2). 303-309 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Aikoh T et al.: "Activation-induced cell death in humna peripheral blood lymhpocytes after stimulation with silicate in vitro" Intermational Journal of Oncology. 12(6). 1355-1359 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hyodoh F et al.: "Release of IL-8 from human monocytes by asbestos" Kawasaki Medical Journal. 24(3-4). 1-10 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Otsuki T et al.: "Soluble Fas message is dominantly expressed in cases with silicosis" Advances in the Prevention of Occup Resp Dis Excerpta Medica International Congress Series ICS. 1153. 896-900 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomokuni A et al.: "Elevated soluble Fas levels in patients with silicosis" Advances in the Prevention of Occup Resp Dis Excerpta Medica International Congress Series ICS. 1153. 931-936 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomokuni A, Otsuki T, Ueki A et al: "Elevated soluble Fas(sFas) levels in silicosis patients in the absence of clinical features of autoimmune diseases or maignant tumors" Cin Exp Immunol. 110. 303-309 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Richelda R Otsuki T et al: "A novel chromosomal translocationt (4;14)(p16.3;p32) in multiple myeloma involves the fibroblast growth-factor receptor 3 gene" Blood. 90. 4062-4070 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Otsuki T Ueki A et al: "Establishment of a new human myeloma cell lines, KMS-18, having t(4;14)(p16.3;p32.3) derived from a case who phenotypically transformed from lg A-λ to BJP-λ and associated with hyperammonemia" Int J Oncol. 12. 545-552 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 植木絢子: "珪酸化合物のスーパー抗原活性" 臨床免疫. 29. 252-258 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Otsuki T, Tomokuni A Ueki A et al: "Soluble Fas message is dominantly expressed in cases with siloosis" Excerpta Med Int Cong Series ICS 1153. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tomokuni A, Otsuki T Ueki A et al: "Elevated soluble Fas levels in patients with siloosis" Excerpta Med Int Cong Series ICS 1153. (in press). (1198)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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